title: Estrogen associated gene polymorphisms and their interactions in the progress of Alzheimer's disease.
abstract: The extensive neuroprotective effects of estrogen against Alzheimer's disease (AD) have been proven in numerous laboratory studies. However, in clinical studies, the exact role of estrogen in AD is still ambiguous. Some evidences even suggested the high levels of estrogen or estrogen replacement treatment increased the risk of AD. Thus, there must be other factors affecting the neuroprotective effects of estrogen. Multiple enzymes and receptor proteins are involved in the biosynthesis, metabolism and signaling pathways of estrogen, and mediate the beneficial effects of estrogen on AD. Previous studies have suggested some polymorphisms of genes encoding these enzymes and proteins are associated with the risk of AD. In addition to the genes associated with estrogen biosynthesis and metabolism and the genes encoding estrogen receptor proteins, some other genes also modulate the effects of estrogen on AD, or interact with other estrogen-associated genes on the progress of AD. The gene-hormone and gene-gene interactions may be key to unraveling the conflicting results regarding the effect of estrogen on AD. In this paper, we will review and discuss the associations between polymorphisms of these genes and their interactions and the susceptibility to AD. A better understanding of these estrogen-associated genes is significant to explore the pathogenesis of AD.
authors.affiliation: Department of Neurology, Xuan Wu Hospital of the Capital Medical University, 45 Changchun Street, Beijing 100053, PR China; Key Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China, 45 Changchun Street, Beijing 100053, PR China. Electronic address: xingyi_211@163.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Xing
authors.forename: J P
authors.initials: JP
authors.lastname: Jia
authors.forename: X J
authors.initials: XJ
authors.lastname: Ji
authors.forename: T
authors.initials: T
authors.lastname: Tian
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000503:physiopathology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D018450:Disease Progression; D004967:Estrogens / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D004967:Estrogens; D003577:Cytochrome P-450 Enzyme System
keywords: 17α-hydroxylase/17, 20-lyase; 17β-HSD; 17β-hydroxysteroid dehydrogenase; 3β-hydroxysteroid dehydrogenase; AAO; ACh; AChE; AD; Alzheimer's disease; ApoE; Aβ; BuChE; COMT; CYP; CYP11A1; CYP17; ChAT; ChE; DHEA; E1; E2; E3; ERT; ESR; Estrogen; FAD; FNC; GSTs; Gene polymorphism; HDL; HSD-3β; LDLr; LRP; MMSE; Mini-Mental State Examination; NCD; RFLP; SULTs; UDP-glucuronosyltransferases; UGTs; VLDLr; VNTR; acetylcholine; acetylcholinesterase; age-at-onset; apolipoprotein E; butyrylcholinesterase; catechol-O-methyltrasferase; choline acetyltransferase; cholinesterase; cytochrome P450; cytochrome P450 cholesterol side chain cleavage enzyme; dehydroepiandrosterone; estradiol; estriol; estrogen receptor; estrogen replacement therapy; estrone; familial Alzheimer's disease; fetal neuroepithelial cell; glutathione-S-transferases; high density lipoprotein; lipoprotein receptor related protein; low density lipoprotein receptor; non-coding deletion; restriction fragment length polymorphism; seladin-1; selective Alzheimer's disease indicator-1; sulfotransferases; variable-number tandem repeat; very low density lipoprotein receptors; β amyloid peptide